Cardiovascular

Pharmacology
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ACE Inhibitors
Mechanism of Action
ACE inhibitors reduce blood pressure by interrupting the
renin-angiotensin aldosterone cycle.
They specifically prevent the conversion of angiotensin I to
angiotensin II, a potent vasoconstrictor.
Reduced formation of angiotensin II decreases peripheral arterial
resistance, thus decreasing aldosterone secretion.
This, in turn, decreases sodium and water retention and decreases
blood pressure. It also decreases systemic vascular resistance
(afterload) and pulmonary capillary wedge pressure (preload), thus
increasing cardiac output in patients with heart failure.

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ACE Inhibitors
Angiotensin-converting enzyme (ACE) inhibitors are used to :
reduce mortality and improve left ventricular function in postacute myocardial infarction (MI) patients.
Prevent adverse left ventricular remodeling, delay progression
of heart failure, and decrease sudden death and recurrent MI.
ACE inhibitors are indicated for suspected
MI and ST segment elevation in two or more precordial leads
Hypertension
Heart failure (without hypotension) in patients not responding
to digoxin or diuretics.
It should also be used when there are clinical signs of acute MI
with left ventricular dysfunction and left ventricular ejection
fraction of greater than 40%.

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ACE Inhibitors
CAPTOPRIL
Captopril (Capoten) is an ACE inhibitor used to treat hypertension and heart
failure.

Dosage

Give 6.25 mg by mouth initially as a single dose; advance to 25 mg three

times per day, and then to 50 mg three times per day as tolerated

Special considerations

Drug may increase serum digoxin and lithium levels, leading to toxicity.
Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) may
decrease drugs antihypertensive effect.
Several weeks of therapy may be required before beneficial effects of
drug are seen.
Overdose of captopril is manifested primarily by severe hypotension.

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ACE Inhibitors
ENALAPRIL
Enalapril (Vasotec) is an ACE inhibitor used to treat hypertension and heart
failure. Enalaprilat (Vasotec I.V.) is the I.V. form of the drug.
Dosage
By mouth: Give 2.5 mg as a single dose initially, and then increase to 20
mg twice per day
I.V.: Give 1.25 mg initially over 5 minutes, then 1.25 to 5 mg every 6 hours
Give drug slowly in I.V. form over at least 5 minutes; may be diluted in 50
ml of compatible solution (such as dextrose 5% in water [D5W], normal
saline solution [NSS] for injection, dextrose 5% in lactated Ringers solution,
D5NSS for injection, or Isolyte E) and infused over 15 minutes
Special considerations
Be aware that patients with diabetes, impaired renal failure, or heart
failure can develop hyperkalemia when given enalapril.
Hyperkalemia can also develop in patients concurrently receiving drugs
that increase serum potassium level.

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ACE Inhibitors
LISINOPRIL
Lisinopril (Prinivil, Zestril) is an ACE inhibitor used to treat hypertension and
heart failure as well as to improve survival rate after acute MI.

Dosage

Hypertension: 20 to 40 mg by mouth daily

For heart failure: 5 mg by mouth daily
For acute MI: 5 mg by mouth within first 24 hours of onset of symptoms,
then 5 mg by mouth after 24 hours, then 10 mg given after 48 hours,
then 10 mg daily for 6 weeks

Special considerations

Use cautiously in patients with impaired renal function because

hyperkalemia may occur.

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ACE Inhibitors
RAMIPRIL
Ramipril (Altace) is an ACE inhibitor used to treat
hypertension and heart failure.

Dosage
Give 2.5 mg by mouth initially as a single dose, and increase to 5 mg
by mouth twice per day as tolerated
Special considerations
Closely assess renal function during the first few weeks of therapy,
especially in patients with severe heart failure or hypertension.

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Adrenergics
DOBUTAMINE HYDROCHLORIDE
Dobutamine (Dobutrex) is an adrenergic, beta1 agonist.
Its indicated to increase cardiac output in cardiac
decompensation situations with systolic blood pressure
of 70 to 100 mm Hg and no accompanying signs of shock.
Action
Dobutamine works by selectively stimulating beta1-adrenergic
receptors to increase myocardial contractility and stroke volume.
This results in increased cardiac output (a positive inotropic effect).
At therapeutic doses,
Decreases peripheral resistance (afterload),
Reduces ventricular filling pressure (preload)
May facilitate atrioventricular (AV) node conduction.
Systolic blood pressure and pulse pressure may remain
unchanged or may be increased from increased cardiac output.

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Adrenergics

DOBUTAMINE HYDROCHLORIDE

Dosage
Give 2 to 20 mcg/kg/minute I.V. infusion, titrated so that cardiac rate isnt greater
than 10% of baseline
Special considerations
Avoid dobutamine administration when systolic blood pressure is less than
100 mm Hg and signs of shock exist. Before utilizing drug therapy, correct
hypovolemia with appropriate plasma volume expanders.
Drug may cause tachycardia, fluctuations in blood pressure, headache, and
nausea.
Dobutamine must be administered by I.V. infusion using an infusion pump or
other device to control flow rate. Hemodynamic monitoring is also necessary to
monitor its effect.
Drug is contraindicated in suspected or known poisoning or drug-induced shock.
When drug is used with beta-adrenergic blockers, increased peripheral resistance
and predominance of alpha-adrenergic effects may occur.
When used with tricyclic antidepressants (TCAs), drug may potentiate pressor
responsemonitor patient closely.
This drug is incompatible with alkaline solutions (sodium bicarbonate).

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Adrenergics
DOPAMINE HYDROCHLORIDE

Dopamine (Intropin) is an adrenergic; its also classified as a vasopressor.

Dopamine is indicated as a secondary drug (after atropine) for symptomatic
bradycardia.
Its also used to treat hypotension (systolic blood pressure greater than or equal
to 70 to 100 mm Hg) accompanied by signs and symptoms of shock.

Action

Dopamine stimulates dopaminergic, beta-adrenergic, and alpha-adrenergic

receptors of the sympathetic nervous system.
It has a direct stimulating effect on beta1- receptors and little or no effect on
beta2-receptors.
Dopamines effects are dose-dependent. In I.V. doses of 0.5 to 5mcg/kg/minute,
it acts on dopaminergic receptors (dopaminergic response),causing vasodilation
in the renal, mesenteric, coronary, and intracerebral vascular beds.
Low to moderate doses (5 mcg/kg/min to 10 mcg/kg/min) produce a beta
effect resulting in cardiac stimulation. In I.V. doses above 10 mcg/kg/minute, it
stimulates alphareceptors resulting in increased peripheral resistance and renal
vasoconstriction.

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Adrenergics

DOPAMINE HYDROCHLORIDE

Dosage
Low dose: 1 to 5 mcg/kg/minute I.V. infusion
(dopaminergic response)
Cardiac dose: 5 to 10 mcg/kg/minute I.V. infusion (beta response)
Vasopressor dose: 10 to 20 mcg/kg/minute I.V. infusion
(alpha response)
Special considerations
Dopamine is contraindicated in uncorrected tachyarrhythmias,
pheochromocytoma, or ventricular fibrillation (VF).
Administer drug into large vein to prevent possibility of
extravasation (central venous access is recommended).
Phentolamine 5 to 10 mg in 10 to 15 ml normal saline solution is used
to infiltrate the area to minimize tissue necrosis if extravasation
occurs in a peripheral site.

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Adrenergics
DOPAMINE HYDROCHLORIDE
Special considerations
Adjust dose to meet individual needs of patient and to achieve
desired response. Reduce dose as soon as hemodynamic condition is
stabilized.
Severe hypotension may result with abrupt withdrawal; taper
gradually.
Hypovolemia should be corrected with appropriate plasma
volume expanders before starting dopamine therapy.
Beta-adrenergic blockers antagonize cardiac effects of dopamine.
Use with phenytoin may cause hypotension and bradycardia.
Dopamine is incompatible with alkaline solutions (sodium
bicarbonate).

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EPINEPHRINE

Adrenergics

Epinephrine is a naturally occurring neurotransmitter adrenergic

used for
Bronchodilator
Vasopressor
cardiac stimulant effects.
Its indicated for
treatment of cardiac arrest (VF, pulseless ventricular
tachycardia [VT], asystole, and pulseless electrical activity
[PEA])
Symptomatic bradycardia (after atropine, dopamine, and
transcutaneous pacing)
Severe hypotension
Severe allergic reactions (when combined with large fluid
volumes, corticosteroids, or antihistamines).

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Adrenergics

EPINEPHRINE
Action
Epinephrine acts directly by stimulating alpha- and betaadrenergic receptors in the sympathetic nervous system.
Its main therapeutic effects include relaxation of bronchial smooth
muscle, cardiac stimulation, and dilation of skeletal muscle
vasculature.
Epinephrine relaxes bronchial smooth muscle by stimulating beta2adrenergic receptors, and constricts bronchial arterioles by
stimulating alpha-adrenergic receptors, resulting in relief of
bronchospasm, reduced congestion and edema, and increased tidal
volume and vital capacity.
As a cardiac stimulant, epinephrine produces positive chronotropic
and inotropic effects by action on beta1-receptors in the heart,
increasing cardiac output, myocardial oxygen consumption, and
force of contraction and decreasing cardiac efficiency.

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Adrenergics
EPINEPHRINE

Dosage
Give 1 mg (10 ml of 1 : 10,000 solution) I.V. every 3 to 5 minutes
during resuscitation; follow each dose with 20-ml I.V. flush; doses up
to 0.2 mg/kg may be considered and used with caution.
For continuous infusion: 1-mg dose (1 ml of 1:1,000 solution) added to
250 ml NSS or D5W; initial dose is 1 mcg/minute and increased to 3
to 4 mcg/minute.
May be given via the endotracheal (ET) tube (if placement is
confirmed) by administering 2 to 2.5 mg diluted in 10 ml NSS; follow
with several positive pressure ventilations.
For profound bradycardia or hypotension: Add 1 mg of 1 : 1000
solution to 500 ml NSS and infuse at 1 to 5 ml/minute for a titrated
dose of 2 to 10 mcg/ minute.

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Adrenergics
EPINEPHRINE
Special considerations
If administered with alpha-adrenergic blockers, vasoconstriction and
hypertensive effects may be counteracted.
If the patient is taking antidiabetics, the effect of the drug may be
decreased; dosage adjustments may be necessary and serum glucose
levels should also be monitored.
Antihistamines and TCAs may potentiate drugs adverse cardiac
effects; avoid concomitant use.
Beta-adrenergic blockers can antagonize drugs cardiac and
bronchodilating effects.
Cardiac glycosides may sensitize the myocardium to drugs effects,
causing arrhythmias.

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Adrenergics
ISOPROTERENOL
Isoproterenol (Isuprel) is an adrenergic used as a cardiac stimulant
and as a temporary measure for treatment of symptomatic
bradycardia if an external pacemaker isnt available.
Its also used to treat Torsade de pointes that doesnt respond to
magnesium sulfate, for temporary control of bradycardia in heart
transplant patients, and for counteracting poisoning from betaadrenergic blockers. Its contraindicated for cardiac arrest.
Action
Isoproterenol acts on beta1-adrenergic receptors in the heart,
producing a positive chronotropic and inotropic effect. It usually
increases cardiac output.
In patients with AV block, isoproterenol shortens conduction time
and the refractory period of the AV node and increases the rate
and strength of ventricular contraction.

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Adrenergics
ISOPROTERENOL
Dosage
1-mg dose mixed in 250 ml D5W and infused at 2 to 10
mcg/minute and titrated to adequate heart rate
For torsade de pointes: Titrate until rhythm is suppressed
Special considerations
Drug is contraindicated in patients with tachycardia caused by
digoxin toxicity, preexisting arrhythmias (other than those that
may respond to treatment with isoproterenol), and angina
pectoris.
Beta-adrenergic blockers antagonize drugs effects; theres an
increased chance of arrhythmias when its used with cardiac
glycosides, potassium-depleting drugs, and other drugs that affect
cardiac rhythm.

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Adrenergics
ISOPROTERENOL
Special considerations
Epinephrine and other adrenergics can cause additive reactions;
drugs may be used together if at least 4 hours elapse between
administration of the two drugs.
Remember that the drug doesnt replace administration of blood,
plasma, fluids, or electrolytes in patients with blood volume
depletion.
Prescription for the I.V. infusion rate should include specific
guidelines for regulating flow or terminating infusion in relation to
heart rate, premature beats, electrocardiogram (ECG) changes,
precordial distress, blood pressure, and urine flow.
Because of danger of arrhythmias, rate of infusion is usually
decreased or temporarily stopped if heart rate exceeds 110
beats/minute. Use with infusion pump.

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Adrenergics

NOREPINEPHRINE
Norepinephrine (Levophed) is an adrenergic indicated for
treatment of severe cardiogenic shock and significant hypotension
(systolic blood pressure less than 70 mm Hg) with low total
peripheral resistance. Its the medication of last resort for
management of ischemic heart disease and shock.
Action
Norepinephrine stimulates alpha- and beta1-receptors within the
sympathetic nervous system. It primarily produces vasoconstriction
and cardiac stimulation.
Dosage
4-mg dose mixed in 250 ml of D5W or D5NSS and titrated to
effect; 0.5 to 1 mcg/minute I.V. usually titrated to improve blood
pressure (up to 30 mcg/ minute may be administered)
Higher dose may be required to achieve adequate perfusion with
poison-induced hypotension

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Adrenergics

NOREPINEPHRINE
Special considerations
Bradycardia, severe hypertension, and arrhythmias may occur.
Alpha-adrenergic blockers may antagonize this drugs effects; avoid
concomitant use.
Dont use this drug with monoamine oxidase inhibitors, methyldopa,
and TCAs; severe hypertension can occur.
Administering norepinephrine isnt a substitute for blood or fluid
replacement therapy. If volume deficit exists, replace fluid before
administering vasopressors.
Monitor extremities for color and temperature.
Administer via a central venous catheter to minimize the risk of
extravasation. Phentolamine 5 to 10 mg in 10 to 15 ml NSS is used to
infiltrate the area to minimize tissue necrosis if extravasation occurs
in a peripheral site.
Norepinephrine is incompatible with alkaline solutions (sodium
bicarbonate).
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Adrenergics
VASOPRESSIN
Vasopressin (antidiuretic hormone, or ADH) is a posterior
pituitary hormone indicated as an alternative vasopressor to
epinephrine in the treatment of adult shock refractory VF.
It isnt recommended for asystole or PEA.
Vasopressin may also provide hemodynamic support in
vasodilatory shock by maintaining coronary perfusion
pressure.
Special considerations
Drug may provoke cardiac ischemia and angina.
Because of the risk of necrosis and gangrene, use extreme caution
to avoid extravasation with this drug.

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Adrenergics
VASOPRESSIN

Dosage
For cardiac arrest: 40 units I.V. push as a one-time dose
Action
Vasopressin acts at the renal tubular level to increase cyclic
adenosine monophosphate (cAMP), which in turn increases water
permeability at the renal tubule and collecting duct. This results in
increased urine osmolality and decreased urine flow rate.
When given at high doses, vasopressin is a powerful
vasoconstrictor of capillaries and small arterioles.

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